Intoxicación grave con nafazolina: puesta al día a partir de un error terapéutico / Severe poisoning with naphazoline: update from a therapeutic error

La nafazolina es un fármaco utilizado como descongestivo, generalmente, en pacientes adultos. Su indicación en pediatría no es frecuente; su uso está aprobado a partir de los 12 años por los efectos tóxicos que posee. La intoxicación en niños genera un cuadro clínico potencialmente grave. Se caracteriza por la aparición inmediata de hipotonía, deterioro del sensorio, hipotermia y bradicardia con grado variable de compromiso clínico. Si bien es una intoxicación infrecuente, la anamnesis y el manejo inicial del paciente son la clave en su evolución. Se presenta a un niño de 4 años que, por un error terapéutico, recibió este fármaco y se destaca la instauración rápida y potencialmente grave del cuadro clínico.

Naphazoline is a drug commonly used as a decongestant in adult patients. Its indication in Pediatrics is not frequent, being approved its use from the age of 12 for the toxic effects it possesses. Intoxication in children generates a potentially serious clinical picture. It is characterized by the immediate appearance of hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise. Although it is an infrequent intoxication, the anamnesis and the initial management of the patient are the key in the evolution. We present a 4-year-old boy who, as a therapeutic error, receives this drug, emphasizing the rapid and potentially severe establishment of the clinical picture.

Determinación de clorhidrato de nafazolina por cromatografía líquida de alta resolución en una solución oftálmica / Naphazoline hydrochloride assay by high performance liquid chromatography in an ophthalmic solution

Introducción: la Farmacopea de los Estados Unidos orienta cómo valorar clorhidrato de nafazolina en una solución oftálmica, pero indica el uso de una columna con grupos nitrilos unidos a sílice porosa, de uso poco frecuente. Objetivo: desarrollar y validar un método alternativo por cromatografía líquida de alta resolución (CLAR) para la cuantificación de clorhidrato de nafazolina en una solución oftálmica. Métodos: el método desarrollado fue de separación isocrática con columna Zorbax SB-C18 (4,6 x 150 mm, 5 µm) y detección ultravioleta a 225 nm. Como fase móvil se empleó solución amortiguadora y acetonitrilo (proporción 85:15, v/v) y la solución amortiguadora fue de KH2PO4 (22 mM) y trietilamina (30 mM), ajustada a pH 3 con ácido fosfórico concentrado. La validación del método se realizó siguiendo las indicaciones de la Guía Q2(R1) de la Conferencia Internacional sobre la Armonización. Se evaluaron los parámetros siguientes: especificidad, precisión, exactitud, linealidad y rango. También se determinó la incertidumbre del método. Resultados: en la especificidad, el placebo no tuvo señal en la zona de clorhidrato de nafazolina; los coeficientes de variación obtenidos para la precisión intermedia resultaron inferiores a 1,5 por ciento; en la exactitud el recobrado fue de 101,52 por ciento y en la linealidad se demostró la ausencia de curvatura en el intervalo 50 a 150 por ciento. La incertidumbre expandida calculada fue un 3 por ciento de la cantidad declarada. Conclusiones: todos los parámetros de validación evaluados se encuentran dentro los límites de aceptación establecidos, por lo que el método es adecuado para los fines propuestos(AU)

Introduction: the United States Pharmacopeia specifies how to titer naphazoline hydrochloride in an ophthalmic solution, but suggests the use of a column with nitrile groups attached to porous silica which is barely used. Objective: to develop and to validate an alternative method by high resolution liquid chromatography for the quantification of naphazoline hydrochloride in an ophthalmic solution. Methods: the developed method was isocratic separation with a Zorbax SB-C18 column (4.6 x 150 mm, 5 µm) and ultraviolet detection set at 225 nm. The mobile phase was buffer and acetonitrile (85:15 ratio, v/v) and the buffer was KH2PO4 (22 mM) and triethylamine (30 mM), adjusted to pH 3 with concentrated phosphoric acid. The validation method was performed pursuant to the Guide Q2(R1) of the International Conference on Harmonization and the following parameters were evaluated: specificity, precision, accuracy, linearity and range. The method uncertainty was also estimated. Results: regarding the specificity, the placebo did not show any signal in the naphazoline hydrochloride zone; the relative standard deviation indexes for intermediate precision were less than 1.5 percent; as to accuracy, the recovery was 101.52 percent and the linearity showed absence of curvature in the 50 to 150 percent range. The estimated expanded uncertainty reached 3 percent of the stated amount. Conclusions: all the validation parameters under evaluation were within the set allowable limits, thus this method is suitable for the intended purposes(AU)

Intoxicación por imidazólicos en pediatría: experiencia del centro de información y asesoramiento toxicológico en niños y adolescentes / Imidazole poisoning in children: experience and poison information center consulting in children and adolescents

Introducción: los derivados imidazólicos del tipo de la nafazolina son utilizados como vasoconstrictores locales, descongestivos nasales y oftálmicos. Su utilización en niños puede ocasionar una intoxicación aguda potencialmente grave. Conocer la epidemiología de esta enfermedad, los aspectos toxicológicos y la forma de presentación clínica puede contribuir a disminuir su incidencia. Objetivos: comunicar la experiencia del Centro de Información y Asesoramiento Toxicológico (CIAT) en menores de 15 años expuestos a imidazólicos y presentar tres casos clínicos de intoxicación por nafazolina asistidos en el Servicio de Emergencia Pediátrica del Hospital Británico (HB).Material y métodos: estudio retrospectivo de las consultas telefónicas por exposición a derivados imidazólicos realizadas al CIAT desde el 1° de enero del 2010 al 31 de diciembre del 2012. Revisión de historias clínicas de tres niños intoxicados por nafazolina asistidos en el 2013 en el HB.Resultados: el CIAT registró 27 casos, edad promedio 2 años y 10 meses. El agente más frecuente fue nafazolina (n=23). La vía intranasal administrado por un familiar, sin indicación médica, y la vía oral por ingesta accidental fueron las circunstancias de exposición más frecuentes. Los tres niños asistidos en el HB se presentaron como pacientes graves. Depresión neuropsíquica, hipotermia, bradicardia, frialdad periférica e hipertensión arterial transitoria o hipotensión, fueron los síntomas predominantes.Conclusiones: el uso de imidazólicos genera riesgo de intoxicación aguda, los niños pequeños son los más afectados, a pesar de la forma típica de presentación clínica puede confundirse con otras patologías. El pediatra es fundamental en la prevención, desaconsejando formalmente su uso.

Introduction: naphazoline type imidazole derivatives are used as local vaso constrictors, nasal and ophthalmic decongestants. Potentially severe acute poisoning in children use is described. Know about the disease epidemiology, toxicological aspects and clinical presentation can contribute to reduce their incidence.Objectives: communicate the experience of the Montevideo Poison Control Center (PCC) in children under 15 years exposed to imidazole derivatives, and present 3 clinical cases of children intoxicated by naphazoline assisted in the pediatric emergency room of the British Hospital (BH). Material and methods: retrospective study of phone consultations by exposure to imidazole derivatives at Montevideo PCC from January 1st of 2010 to December 31st of 2012. Medical records review of 3 poisoned children by naphazoline assisted in 2013 in the BH.Results: Montevideo PCC registered 27 cases, with average age of 2 years and 10 months. Naphazoline was the most frequent agent involved (n = 23). Intranasal route administered by a family member without medical indication, and non-intentional ingestion were the most frequent circumstances of exposure. The three children assisted in the BH emergency department were serious ill patients. Depression of consciousness, altered mental status, peripheral hypoperfusion, hypothermia, bradycardia and transient hypertension or hypotension, were the predominant symptoms. Conclusions: use of imidazolic derivatives generates great risk of acute intoxication. Young children are the most affected despite the typical form of clinical presentation can be confused with other severe diseases. The pediatrician has a critical role in preventing formally and discouraging its use.

Simultaneous determination of naphazoline hydrochloride, chlorpheniramine maleate and methylene blue in their ternary mixture

Validated spectrophotometric and chemometric methods were developed for determination of Naphazoline Hydrochloride [NAP], Chlorpheniramine maleate [CLO] and Methylene blue [MB] in their ternary mixture. Method A was a spectrophotometric method, where NAP and MB were determined using second derivative [D2] spectrophoto metric method using the peak amplitudes at 299 nm and 337 nm for NAP and MB respectively, while CLO was determined using second derivative ratio [DD[2]] spectrophotometric method using the peak amplitude at 276.6 nm. Method B used the chemometric techniques; principal component regression [PCR] and partial least squares [PLS] for determination of NAP, CLO and MB using the information contained in the absorption spectra of their ternary mixture solutions. The proposed methods have been successfully applied for the analysis of NAP, CLO and MB in their pharmaceutical formulation and the obtained results were statistically compared with the reported methods

A case of borderline clear cell fibroadenoma / 대한산부인과학회지

Clear cell tumor of borderline malignancy has been reported to account for 5 to 8% of all clear cell neoplasms, and <1% of borderline malignancies of the ovary. Borderline clear cell fibroadenoma with or without microinvasion mostly occurs in women with middle age, and the presenting symptoms associated with this tumor are non-specific. The clinico-pathologic features of borderline clear cell fibroadenoma are not well known because of its rarity. Furthermore, there is no consensus for treating the disease. Thus, we report a case of borderline clear cell fibroadenoma presenting as ovarian fibroadenoma with a review of literature.

Efficacy of ketotifen fumarate 0.025% eye drops in treatment of vernal keratoconjunctivitis

This prospective hospital-based study has been conducted to evaluate the efficacy of ketotifen fumarate 0.025% eye drops in controlling the signs and symptoms of vernal keratoconjunctivitis and to compare its effect with that of commonly used combination of eye drops for vernal keratoconjunctivitis both in mild and severe cases. A total of 20 patients [40 eyes] who came to the outpatient clinics at the ophthalmology department at King Hussein Medical Center were selected during the period between January 2004 and May 2004. They were diagnosed to have vernal keratoconjunctivitis with no other ocular or systemic pathologies that might affect the results. Two groups of medications were used; ketotifen for the right eye and naphazoline with antazoline and sodium cromoglycate for the left eye. Steroids were used for both eyes at the beginning to establish a primary control and added if needed later. The patients were followed up and given scores for their signs and symptoms on the first visit and on each follow up visits, which were distributed over a period of 6 weeks. Further division of the population into two subgroups of mild and moderate-severe groups as the behavior of the drugs differs in each group of the two. Generally, similar behavior of the disease was noticed in the two groups of medications, particularly in the mild cases where ketotifen alone could achieve a satisfactory final result as that of the combination of sodium cromoglycate and naphazoline with antazoline. The improvement was noticed in all signs and symptom studied [itching, watery discharge, redness photophobia, hyperemia, papillae and corneal signs of vernal keratoconjunctivitis]. In mild cases, there was no significant difference between the two groups of medications [p>0.05]. Steroids could be avoided in the mild cases. In the severer cases, ketotifen alone was not enough in controlling the signs and symptoms and steroids were needed at frequent intervals. In severe cases the improvement was significantly better in the group using ketotifen fumarate in the symptoms of watery discharge and redness, and in the hyperemia sign [p<0.05], while other symptoms and signs improved in both groups of medications without significant difference [p>0.05]. The use of ketotifen is of an advantage over the combination of naphazoline 0.025% with antazoline 0.5%, and sodium cromoglycate 4% as it is only one bottle with a lower frequency of instillation, thus the compliance would be better, although it almost has the same price as the other two combined. The use of ketotifen is convenient for patients with mild symptoms as a solo drug after few days of steroids. In the severe cases, ketotifen alone could not be used without frequent intervals of steroids, although a significant improvement in this group was noticed over the group of combined medications in watery discharge and redness symptoms and hyperemia sign

P21 and p53 expression in patients with epithelial ovarian carcinoma / 대한산부인과학회지

OBJECTIVE: Mutations in p53 are the most common genetic alterations in human malignancies. Expression of its protein product has been linked to decreased survival rate in ovarian carcinoma. P53 is well known as a pro-apoptotic tumor suppressor gene, but less is known about the importance of p21 expression in patients with epithelial ovarian malignancies. The purpose of this study was to investigate the different expression levels of p53 and p21 in various cell type of epithelial ovarian carcinomas and to determine their clinical significances. METHODS: Fifty eight patients (serous (n=18), mucinous (n=14), clear cell (n=12), endometrioid (n=14) carcinoma) with epithelial ovarian carcinoma were studied using paraffin-embedded tissue specimens. Immunohistochemical staining utilizing monoclonal antibody against p21 and p53 were performed. Amount of their proteins were quantified using western blotting. RESULTS: Mean age was 49.2 years old and advanced stage (III and IV) of cancer were 26 (44.8%). Recurrence rate and death rate were 20.7%, 22.4% respectively. With immunohistochemical staining for p21 and p53, p53 were significantly strongly stained in almost all epithelial ovarian carcinomas. However, p21 expressions were found in 10% of patients with serous carcinoma, 14% of patients with mucinous carcinoma, 38% of patients with endometrioid carcinoma, but 100% of patients with clear cell carcinoma. Among the patients whose tumors showed p21 staining, over expression were found in all clear cell typein western blot. But positive staining for p21 was below 10% in each slides of serous, mucinous and endometrioid type of ovarian carcinoma except clear cell type. This finding suggest that P21 expression was independent pathway in cell cycle regulation and apoptosis to the expression of p53 in serous, mucinous, and endometrioid type of ovarian carcinoma, but showed strongly positive correlation P21 and p53 expression in clear cell carcinoma. CONCLUSION: P21 may be used as a marker for confirmation of diagnosis of clear cell carcinoma due to its unique expressions of p21.

Hemorrhagic stroke after naphazoline exposition: case report

Dez por cento de todos os eventos vasculares encefálicos são devido às hemorragias intracerebrais espontâneas, associados a drogas (lícitas e ilícitas) em 9,5% de todos os casos em adultos jovens. Relatamos o caso de um homem de 44 anos de idade, sem doenças prévias, que apresentou cefaléia súbita e hipertensão arterial 24 horas após o uso de congestionante nasal contendo nafazolina. A tomografia de crânio evidenciou hemorragia talâmica. Durante a investigação não foram encontrados outros fatores de risco e a hemorragia foi atribuída à exposição à nafazolina.

Exposiçäo aguda a derivados imidazolínicos em crianças / Acute exposure to imidazoline derivatives in children

OBJETIVOS: Estudar a exposiçäo aguda a derivados imidazolínicos em crianças com idade inferior a 15 anos, atendidas no período de janeiro de 1994 a dezembro de 1999. MÉTODOS: Neste estudo retrospectivo foram avaliadas 72 crianças com idades entre dois meses e 13 anos, mediana de dois anos (25 por cento a 75 por cento; um a três anos), expostas a nafazolina (n = 48), fenoxazolina (n = 18), oximetazolina (n = 5) e tetrizolina (n = 1); por via oral (n = 46), nasal (n = 24) ou desconhecida (n = 2). RESULTADOS: No total, 57 crianças desenvolveram manifestações clínicas: sonolência (n = 34), sudorese (n = 20), palidez (n = 17), hipotermia (n = 16), bradicardia (n = 13), extremidades frias (n = 9), agitaçäo (n = 7), taquicardia (n = 6), vômitos (n = 34), respiraçäo irregular e apnéia (n = 5), miose/midríase (n = 4), sendo a nafazolina (n = 47), a fenoxazolina (n = 5) e a oximetazolina (n = 4) os princípios ativos mais envolvidos. O início das manifestações clínicas foi rápido, iniciando-se, em 32/57 crianças, até duas horas após a exposiçäo. Somente medidas de suporte foram empregadas, com uma criança necessitando de ventilaçäo mecânica após exposiçäo à nafazolina. Na maioria dos pacientes, o quadro clínico remitiu até 24 horas após a exposiçäo (n = 39/57). Näo houve evoluçäo letal. Pacientes expostos à nafazolina (n = 47/48) apresentaram maior freqüência de manifestações clínicas de intoxicaçäo em comparaçäo com aqueles expostos à fenoxazolina (n = 5/18) (p < 0,001). Comparando-se a freqüência de pacientes que desenvolveram manifestações clínicas de acordo com a via de exposiçäo (oral, n = 34/46; nasal, n = 21/24), näo foi encontrada uma diferença estatisticamente significante (p = 0,31). CONCLUSÕES: Na maioria dos casos de exposiçäo a derivados imidazolínicos, principalmente à nafazolina e em crianças com menos de três anos de idade, ocorreu, independentemente da via (oral ou nasal), o aparecimento precoce de manifestações clínicas de intoxicaçäo, destacando-se as depressöes neurológica, cardiovascular e respiratória, que regrediram até 24 horas após a exposiçäo

The Therapeutic Effect of Nail Splinting in Ingrown Toenails / 대한피부과학회지

BACKGROUND: Ingrown toenail is one of the most common nail complaints. It occurs chiefly on the great toes, where there is an excessive lateral nail growth into the nail fold, leading to painful irritation, inflammation, infection, and growth of excessive granulation tissue. Many treatments have been described, but these classic treatment modalities may lead to severe damage of the nail fold or to frequent relapses. OBJECTIVE: We attempted to evaluate the therapeutic effect of nail splinting which is a noninvasive therapy for ingrown toenails. METHODS: A total of 64 patients(78 lesions) with ingrown toenails were enrolled in the study. The lateral edge of the nail plate including the spicule is splinted with a lengthwise-incised flexible plastic tube. The efficacy of nail splinting for ingrown toenail was assessed by analyzing the degrees of post-treatment pain and a recurrence rate. RESULTS: 1.The average age of the patients was 37 years old. There were 38 male patients(47 lesions) and 26 female patients(31 lesions). The right big toe was affected in 27 patients and the left big toe in 23 patients. Fourteen patients had both feet affected at the same time. 2.The pain all cleared in an average 2.3 days of treatment. Other problems such as redness, swelling and granulation tissue gradually decreased as time went by. 3.There was a 7.8% recurrence rate at six months after the procedure. CONCLUSION:We recommend nail splint as an alternative to traditional treatment for ingrown toenail because it is simple and easy to perform, noninvasive, effective, well tolerated, and does not require any special equipment.

Clinical Significance of serum Endothelin-1 and Interleukin-8 in Sepsis / 결핵

BACKGROUND: Sepsis is a clinical syndrome characterized by a systemic inflammatory and hemodynamic response to severe bacterial infections that involve various mediators. Endothelin (ET)-1, a potent vasocon strictor is associated with multiple organ failure, and interleukin (IL)-8, a proinflammtory cytokine, plays a major role in neurophil activation. Both have been reported to be useful parameters in the clinical assessment of sepsis. The levels of ET-1 and IL-8 in the blood were measured in patients with sepsis, and the correlation of both parameters and their relationship with the clinical data was assessed. METHODS: 19 sepsis patients and 17 controls were studied. Blood samples of the sepsis patients were drawn in day 1, 3, 7, and 14. the APACHE III scores were calculated in concurrent days. The ET-1 and IL-8 levels were measured using immunoassay methods. RESULTS: The ET-1 levels of patients with sepsis were significantly higher than in the controls. In patients with sepsis, non-survivors had higher ET-1 levels than survivors on day 1 and 7, and patients with shock also had higher ET-1 levels than normotensive patients on admission. The ET-1 levels were significantly correlated wit the creatinine levels in day 1, 7, and 14. The IL-8 levels showed a significant correlation with the ET-1 levels on day 14. CONCLUSION: ET-1 was found to be closely related with the clinical outcome, shock, and renal failure, and showed a correlation with IL-8. these mediators can be considered not only to play pathophysiologic roles but also as useful parameters in the clinical assessment of sepsis.

Biologic changes of implants and grafts in rhinoplasty / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: An array of materials have been used for rhinoplasty, however, the fate of these materials after rhinoplasty is not all clear. This study was performed to find post-operative gross and microscopic changes of the implants and grafts (cartilage, Gore-Tex , and Alloderm), and to guide selection of implants and graft. MATERIALS AND METHODS: We took the implants and grafts out from nine patients who underwent revision rhinoplasty for cosmetic problems, and studied gross and microscopic charaterizations. RESULTS: Autologous cartilages showed minor volume reduction and remodeling in gross examination, and mild degeneration, peripheral fibrosis, and fibroblast in-growth without inflammation under microscopic examination. Gore-Tex , which was a little difficulty to remove, had good volume preservation with focal in-growth of fibroblasts and inflammatory cells. A gross examination of Alloderm showed preserved volume, but thin, soft and weak appearance. A microscopic examination of Alloderm showed well preserved collagen materials without inflammation. CONCLUSIONS: Cartilages have good biocompatibility and stabilization, but it is necessary to study absorption and remodeling. We found that Gore-Tex is a good volume filler for dorsal augmentation, whereas Alloderm is a good material for camouflage.

Familial Lupus Erythematosus Occurred in Mother and Son / 대한피부과학회지

The pathogenesis of lupus er thematosus(LE) appears to be multifactorial, including genetic, hormonal and environmental influences. Genetic factors have long been suspected to an important role in its pathogenesis. This was been shown in family studies and twin studies. We report a family in which mother developed SLE and son developed DLE. The mother, 35 year old female, had hyperpigmcnted brownish macules and atrophic scars on the face and also complained of fever, chill and arthralgia for 2 years. The clinical, laboratory and histopathological findings showed characteristic features of systemic lupus erythematosus. she had been treated with systemic prednisolone, hydrcxychloroquin sulfate and topical corticosteroid ointment for about 4 years resulting favorable improvement skin lesions. Laboratory studies during her course had demonstrated persist leukopenia, peckled pattern ANA and VDRL positive. The son, 10-year-old, had peasized, multiple erythematous papules and plaques on the face and arms for 2 months. The lirical, laboratory and histopathological findings showed characteristic features of discoid lupus erythematosus. He was treated with systernic prednisolone for 2 years, hydroxychloroquin sulfate and topical corticosteroid ointment for abcut 4 years resulting nearly all clearing of skin lesions with slighthly hyperpigmentation. Laboratory studies during his course had demonstrated only weakly ANA positive.

Prevention of rhinitis medicamentosa

We report the histological and histochemical changes of the respiratory mucosa of the guinea pigs nasal cavity after nasal instillation by decongestant 0.05% Naphazoline Hydrochloride drops under conditions of feeding of normal diet and by adding additional quantities of vitamin C and B[2]. The results revealed that the nasal instillation by 0.05% Naphazoline can provoke a series of histological and histochemical changes in the respiratory mucosa of guinea pigs nasal cavities, but all these changes can be reduced significantly by increasing the supply of vitamin C and B[2] in the feeding of the animals

Angina variante asociada al uso de un descongestionante nasal / Varying angina associated to the use of a nasal anticongestive agent

Se comunica la observación de un paciente que hace episodios de angina variante con taquicardia ventricular polimorfa, en relación a inhalación de nafazolina, como descongestionante nasal. Este caso plantea la eventualidad de que un medicamento de uso corriente, como estos preparados de pretendida acción local, pueda desencadenar arritmias severas, consecutivo a un espasmo coronario en individuos susceptibles, particularmente si presentan lesiones coronarias, por discretas que éstas sean

Histochemical study on the behavior of glycogen and total lipids in pregnant albino rats and their progenies treated with naphazoline

The histochemical study of 25 pregnant rats liver submitted to nasal drop instillation of saline and naphazoline at increasing concentrations, at the 19th day pregnancy, showed glycogen decrease and total lipid increase, only at a concentration of 1:1,000 of naphazoline. In this group occured also an increase of fetal liver lipids.